Title
Tolerization of an established αb-crystallin-reactive T-cell response by intravenous antigen
Author
Verbeek, R.
van der Mark, K.
Wawrousek, E.F.
Plomp, A.C.
van Noort, J.M.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire against self-antigens is likely to be more relevant than the potential reactivity of naive T cells. Methods to eliminate such an established T-cell response are less well understood. In this study, we explored the effectiveness of intravenous soluble antigen to eliminate a pre-existing T-cell response against αB-crystallin, a candidate autoantigen in MS. We used mice that are deficient for the target antigen. This condition allowed for a vigourous T-cell and antibody response to develop upon immunization, and eliminated all possible endogenous mechanisms of tolerance for αB-crystallin that are found in normal rodents. When applied 3 weeks after priming with αB-crystallin, intravenous administration of soluble antigen almost completely abrogated the established T-cell response in a dose-dependent manner as evidenced by T-cell non-responsiveness in tolerized animals to a re-challenge with antigen in complete Freund's adjuvant. Evaluating delayed-type hypersensitivity responses after tolerance induction revealed that the tolerizing effect was achieved within 24 hr. Furthermore, the tolerizing effect was found to be antigen-specific and long lasting. In contrast, serum antibody levels were markedly increased. Our data clarify that in the absence of any natural form of immune regulation, antigen-specific memory/effector T cells can be effectively silenced by intravenous antigen. © 2007 Blackwell Publishing Ltd.
Subject
Biology
Biomedical Research
αB-crystallin
Autoimmunity
Multiple sclerosis
T cells
Tolerance
alpha crystallin
alphab crystallin
antibody
autoantigen
Freund adjuvant
ovalbumin
epitope
gamma interferon
immunoglobulin G
recombinant protein
animal cell
animal experiment
antibody blood level
antibody response
antigen specificity
article
cellular immunity
controlled study
delayed hypersensitivity
dose response
drug dose comparison
drug efficacy
immune response
immunization
immunological tolerance
immunoregulation
mouse
multiple sclerosis
nonhuman
priority journal
protein deficiency
T lymphocyte activation
animal
biosynthesis
cell culture
dendritic cell
immunology
intravenous drug administration
lymphocyte activation
T lymphocyte subpopulation
time
alpha-Crystallin B Chain
Animals
Autoantigens
Cells, Cultured
Dendritic Cells
Dose-Response Relationship, Immunologic
Epitopes
Hypersensitivity, Delayed
Immune Tolerance
Immunoglobulin G
Injections, Intravenous
Interferon Type II
Lymphocyte Activation
Mice
Multiple Sclerosis
Recombinant Proteins
T-Lymphocyte Subsets
Time Factors
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DOI
https://doi.org/10.1111/j.1365-2567.2007.02592.x
TNO identifier
240065
ISSN
0019-2805
Source
Immunology, 121 (3), 416-426
Document type
article